HER2-neu status as a predictor of survival in patients with brain metastases from primary breast adenocarcinoma

Abstract

1016 Background: Recent data suggests that Her2-neu positivity predicts for development of brain metastases in patients with breast cancer. However, there now exists a targeted agent, trastuzumab, that provides excellent systemic control of Her2-positive (Her2 +) disease. We therefore explore the course of this disease as a function of Her2 status in patients with primary breast cancer who have developed brain metastases. Method: We retrospectively analyzed data from 50 consecutive patients with primary breast cancer who subsequently developed brain metastases. Factors evaluated included Her2-neu, ER/PR, T stage, nodal stage, use of whole brain radiotherapy (WBRT) as initial management of CNS disease, initial number of metastases, hormonal therapy, use of trastuzumab, and Karnofsky Performance Status (KPS). Overall survival (OS) was modeled using Cox proportional hazard. Kaplan-Meier analysis was used for significant predictors. Results: Median age was 49 years (28–78 y). Fifty-four percent of patients were Her2 +, whereas only 15% were ER +. All but one Her2 + patient received trastuzumab. Seventy-two percent were node positive, and only 5 patients were metastatic at time of diagnosis. T stage was as follows: T1 = 24%, T2 = 36%, T3 = 8%, and T4 = 16%. Adjuvant chemotherapy was administered to 90% of the sample, and 94% underwent radiation to the primary site. Sixty-six percent had <= 3 initial brain metastases, and 38% underwent WBRT as part of their initial CNS management. Median followup was 55 weeks. A Cox multivariate model of OS yielded two independent predictors. Her2 positivity (p = 0.007) and <= 3 initial brain metastases (p = 0.003) were associated independently with OS from time of initial diagnosis of CNS disease. Median survival and actuarial one year survival for Her2 + patients were 65 weeks and 87%, respectively, versus 33 weeks and 44% for Her2 negative patients (Mantel Cox p = 0.025). Conclusions: Although Her2 + patients appear to have a greater risk of developing brain metastases, overall survival from time of initial diagnosis of brain metastasis appears to be better in this cohort. This may be a function of the improved extracranial control provided by trastuzumab in patients with Her2+ disease. No significant financial relationships to disclose.